TY - JOUR T1 - Long-Term Neural Correlates of Reversible Fear Learning in the Lateral Amygdala JF - The Journal of Neuroscience JO - J. Neurosci. SP - 16845 LP - 16856 DO - 10.1523/JNEUROSCI.3017-12.2012 VL - 32 IS - 47 AU - Bobae An AU - Ingie Hong AU - Sukwoo Choi Y1 - 2012/11/21 UR - http://www.jneurosci.org/content/32/47/16845.abstract N2 - Fear conditioning and extinction are behavioral models that reflect the association and dissociation of environmental cues to aversive outcomes, both known to involve the lateral amygdala (LA). Accordingly, responses of LA neurons to conditioned stimuli (CS) increase after fear conditioning and decrease partially during extinction. However, the long-term effects of repeated fear conditioning and extinction on LA neuronal firing have not been explored. Here we show, using stable, high signal-to-noise ratio single-unit recordings, that the ensemble activity of all recorded LA neurons correlates tightly with conditioned fear responses of rats in a conditioning/extinction/reconditioning paradigm spanning 3 d. This CS-evoked ensemble activity increased after conditioning, decreased after extinction, and was repotentiated after reconditioning. Cell-by-cell analysis revealed that among the LA neurons that displayed potentiated responses after initial fear conditioning, some exhibited weakened CS responses after extinction (extinction-susceptible), whereas others remained potentiated (extinction-resistant). The majority of extinction-susceptible neurons exhibited strong potentiation after reconditioning, suggesting that this distinct subpopulation (reversible fear neurons) encodes updated CS–unconditioned stimulus (US) association strength. Interestingly, these reversible fear neurons displayed larger, more rapid potentiation during reconditioning compared with the initial conditioning, providing a neural correlate of savings after extinction. In contrast, the extinction-resistant fear neurons did not show further increases after reconditioning, suggesting that this subpopulation encodes persistent fear memory representing the original CS–US association. This longitudinal report on LA neuronal activity during reversible fear learning suggests the existence of distinct populations encoding various facets of fear memory and provides insight into the neuronal mechanisms of fear memory modulation. ER -